The Gene for PAX7, a Member of the Paired-Box-Containing Genes, Is Localized on Human Chromosome Arm 1p36

The murine Pax-7 gene and the cognate human gene, formerly designated HuP1, are members of the multi-gene paired-box-containing class of developmental regulatory genes first identified in Drosophila. By analysis of somatic cell hybrids segregating human chromosomes, the gene encoding PAX7 was localized to human chromosome 1. Fluorescence in situ hybridization confirmed this assignment and allowed mapping of the gene to the terminal region of the short arm (1p36) of the chromosome. Additionally, these results confirm the extensive homology between human chromosome 1p and the distal segment of mouse chromosome 4, extending from bands C5 through E2.     

Chromosomal localization of phospholipase A2 activating protein, an Ets2 target gene, to 9p21

A murine Ets2 target gene isolated by differential display cloning was identified as the phospholipase A2 activating protein (PLAA) gene. A 2.7-kb human cDNA demonstrating high homology to mouse and rat Plaa genes was then isolated and characterized. Human PLAA contains six WD-40 repeat motifs and three different protein kinase consensus domains. Fluorescence in situ hybridization (FISH) mapping placed PLAA on chromosome 9p21, a region frequently deleted in various cancers. A comprehensive mapping strategy was employed to define further the chromosomal localization of PLAA relative to CDKN2A within the 9p21 locus. Radiation hybrid mapping placed the gene 7.69 cR from WI-5735 (LOD >3.0), a marker in close proximity to CDKN2A and CDKN2B. Yeast artificial chromosome (YAC) mapping localized PLAA proximal to the CDKN2A/CDKN2B genes and to a region flanked by D9S171 and INFA commonly deleted in many neoplasms. Two YACs contained both PLAA and D9S259, a marker present in a second more proximal minimal deleted region observed in cutaneous melanoma and squamous cell lung carcinoma. Double-color fiber FISH mapping confirmed the location of PLAA centromeric to D9S171 and CDKN2A/CDKN2B. The mapping data suggest a possible tumor suppressor role for this gene.     

Physical mapping of the bovine, caprine and ovine homologues of the paired box gene PAX8.

The PAX8 gene, a member of the human paired box gene family, was mapped by FISH to chromosome 11 in cattle and goat and to the short arm of chromosome 3 in sheep. The cytogenetic position of PAX8 on BTA 11 and on its homologue OAR 3p lies in the region where the interleukin beta (IL1B) gene has been previously located, (BTA 11q22. 1-->q22.3 and OAR 3p25-->q26 respectively; Lòpez-Corrales et al., 1998). The results indicated that PAX8 as well as interleukin beta and interleukin alpha (IL1B and IL1A) genes detected on the human chromosome segment HSA 2q13-->q21 maintain a similar order and location in these three related species. In addition, the breakpoint in conserved synteny can now be narrowed to a position between the protein C (PROC) and PAX8 genes, which lie in close proximity on HSA 2.     

Chromosomal localization of two human zinc finger protein genes, ZNF24 (KOX17) and ZNF29 (KOX26), to 18q12 and 17p13-p12, respectively

Two members of the zinc finger Krüppel family, ZNF24 (KOX17) and ZNF29 (KOX26), have been localized by somatic cell hybrid analysis and in situ chromosomal hybridization to human chromosomes 18q12 and 17p13-p12, respectively. The mapping of ZNF29 together with the previously reported localization of ZFP3 suggests that a zinc finger gene complex is located on human chromosome 17p. ZNF29 maps centromeric to the human p53 tumor antigen gene (TP53). In the analogous murine position, the two mouse zinc finger genes Zfp2 and Zfp3 have recently been assigned to the distal region of mouse chromosome 11, the murine homolog of human chromosome 17. Both human zinc finger genes ZNF24 and ZNF29 are in chromosomal regions that have been noted to be deleted in neoplasms of the lung and of the central nervous system at chromosome 17p and in colorectal neoplasia at chromosomes 17p and 18q.     

Pax-5 is expressed at the midbrain-hindbrain boundary during mouse development.

The murine paired-box-containing gene 5, Pax-5, is highly homologous to two other Pax genes, Pax-2 and Pax-8. The expression pattern of Pax-5 during mouse embryogenesis was examined by in situ RNA hybridization and compared to those of Pax-2 and Pax-8. Beginning at day 9.5 postcoitum (p.c.), Pax-5 was expressed in the developing brain, predominantly at the midbrain-hindbrain boundary, and in the neural tube. While the neural tube expression pattern overlapped completely with Pax-2 and Pax-8, the expression pattern in the brain was only partially overlapping. Unlike Pax-2 and Pax-8, Pax-5 was not expressed in the developing excretory system, thyroid, eye or ear. Our data suggest that Pax-5 has a role in the development of the central nervous system.     

Chromosomal location of murine and human IL-1 receptor genes.

The gene for the type I interleukin-1 (IL-1) receptor has been mapped in both mouse and human. In the human genome, a combination of segregation analysis of rodent-human hybrid cells and chromosomal in situ hybridization has placed the gene on the long arm of chromosome 2, at band 2q12. This is near the reported map position of the loci for IL-1 alpha and IL-1 beta (2q13----2q21). The murine gene has been mapped by analysis of restriction fragment length polymorphisms in interspecific backcrosses to the centromeric end of chromosome 1, in a region that is syntenic to a portion of human chromosome 2. The murine Il-1r1 gene has thus been separated from the IL-1 genes, which lie on murine chromosome 2.     

Localization of the human oncogene SPI1 on chromosome 11, region p11.22

Summary Spi1 is an oncogene specifically activated in acute murine erythroleukemias induced by the Friend spleen focus forming virus (SFFV). Three probes were used for the chromosomal assignment of the human SPI1 oncogene: cDb1 and RaB2 correspond respectively to murine Spi1 and human SPI1 cDNA probes; C45a6B probe is a murine genomic DNA sequence located in the Spi1 5 region and is known as a major SFFV integration site in murine erythroleukemia cells. Somatic hybrid cells enabled cDb1 and RaB2 to be assigned to chromosome 11. The murine C45a6B probe, which is not included in the Spi1 gene, detected a homologous sequence on human chromosome 11. RaB2 was assigned to 11p 11.22 by in situ hybridization. Three human genes known between 11p11 and 11p13 (FSHB, CAT, ACP2) were on murine chromosome 2. Therefore, the localization of human SPI1 on 11p11.22 was consistent with the assignment of the Spi1 oncogene to murine chromosome 2.The nomenclature used in this paper conforms to the recommendations of Human Gene Mapping 10 (1989); for man SPI1, for mouse Spi1     

Chromosomal assignments of the genes for neuroendocrine convertase PC1 (NEC1) to human 5q15-21, neuroendocrine convertase PC2 (NEC2) to human 20p11.1-11.2, and furin (mouse 7[D1-E2] region).

The chromosomal localization of the genes coding for the pro-protein and pro-hormone convertases PC1, PC2, and Furin has been achieved by in situ hybridization. The genes for PC1 and PC2 were located on human chromosomes 5q15-21 and 20p11.1-11.2, respectively. The gene for Furin was assigned to the mouse chromosome 7D1-7E2 region. These data complete the chromosomal localization of these three convertases in both human and mouse. The results confirm the regional correspondence of the human chromosomes 15 and mouse chromosomes 7, as well as between human chromosome 20 and mouse chromosome 2. Furthermore, the identification of the NEC1 locus on human chromosome 5 and mouse chromosome 13 suggests a conservation of synthenic regions between these regions of the human and mouse genomes.     

Chromosomal localization of SLC12A5/Slc12a5, the human and mouse genes for the neuron-specific K(+)-Cl(-) cotransporter (KCC2) defines a new region of conserved homology.

K(+)-Cl(-) cotransporters (KCCs) constitute a branch of the cation-chloride cotransporter (CCC) family. To date, four KCC isoforms (KCC1-KCC4) have been identified and they all mediate obligatorily coupled, electroneutral transmembrane movement of K(+) and Cl(-) ions. KCC2 (gene symbol SLC12A5) is expressed exclusively in neurons within the central nervous system and abnormalities in its expression have been proposed to play a role in pathological conditions such as epilepsy and neuronal trauma. Here we have determined chromosome location of both the human and the mouse genes encoding KCC2, which may assist in future efforts to determine the contribution of KCC2 to inherited human disorders. We assigned human SLC12A5 to 20q12-->q13.1 and its murine homolog, Slc12a5, to 5G2-G3 by fluorescence in situ hybridization (FISH). These mapping data are contradictory to the previously reported human-mouse conserved synteny relationships disrupting an exceptionally well-conserved homology segment between human Chr 20 and mouse Chr 2. We hence suggest the first region of conserved homology between human Chr 20 and mouse Chr 5.     

Physical mapping of the genes for three components of the mouse DNA replication complex: polymerase alpha to the X chromosome, primase p49 subunit to chromosome 10, and primase p58 subunit to chromosome 1

DNA polymerase alpha and primase are two key enzymatic components of the eukaryotic DNA replication complex. In situ hybridization of cloned cDNAs for mouse DNA polymerase alpha and for the two subunits of mouse primase has been utilized to physically map these genes in the mouse genome. The DNA polymerase alpha gene (Pola) was mapped to the mouse X chromosome in region C-D. The gene encoding the p58 subunit of primase (Prim2) was located to mouse chromosome 1 in region A5-B and the p49 subunit gene (Prim1) was found to be on mouse chromosome 10 in the distal part of band D that is close to the telomere. Current knowledge of mouse and human conserved chromosomal regions along with the findings presented here lead to predictions of where the genes for the DNA primase subunits may be found in the human genome: the p58 subunit gene may be on human chromosome 2 and the p49 subunit gene on human chromosome 12. The mapping of Pola to region C-D of the mouse X chromosome adds a new marker in a conserved region between the mouse X chromosome and region Xp21-22.1 of the human X chromosome.     

Genomic construct and mapping of the gene for CMAP (leukocystatin/cystatin F, CST7) and identification of a proximal novel gene, BSCv (C20orf3)

It is proposed that CMAP (leukocystatin/cystatin F, HGMW-approved symbol CST7) expression is correlated with the metastatic potential of malignant tumors. FISH analysis of human and murine CMAP revealed the genomic loci 20p11.21-p11.22 of the human family 2 cystatin cluster and mouse chromosome region 2G1-G3, respectively. Like murine CMAP, the human CMAP gene is constructed from four divided exons, all of which encode the functional domains of the putative translational product. Based on the computational analysis, a novel gene weakly similar to the plant strictosidine synthase, named BSCv (HGMW-approved symbol C20orf3), was identified on the opposite allele at a distance of a few kilobases from the human CMAP gene. In between human CMAP and the BSCv gene, there is a unique tandem repeat sequence. CpG-rich island characteristics and GC-box features normally observed in housekeeping genes were not seen around exon 1 of the CMAP gene, reflecting the restricted expression of CMAP in hematopoietic cells.     

Mouse phosphoinositide 3-kinase p110alpha gene: cloning, structural organization, and localization to chromosome 3 band B.

Phosphoinositide 3-Kinases (PI3-Kinases) are a family of dual specificity enzymes with a unique lipid kinase activity toward the D-3 position of the inositol ring of phosphoinositides and a less well characterized serine/threonine protein kinase activity. Class IA PI3-Kinases comprise a 110-120 kDa catalytic subunit (usually termed p110) and an 85 kDa or 50 to 55 kDa regulatory subunit (often called p85). cDNAs for three mammalian Class IA PI3-Kinase catalytic subunits designated p110alpha, p110beta, and p110delta have been cloned from several species. A YAC clone for the human p110alpha gene has also been cloned and mapped to chromosome 3q26.3. However, structural organization for any of the PI3-Kinase p110alpha genes has not been reported. Here, we report the cloning, structural organization, and chromosomal localization of the mouse PI3-Kinase p110alpha gene. The translated portion of the mouse p110alpha gene is encoded by 19 exons that span at least 24 kb. Dual color fluorescence in situ hybridization (FISH) was performed to determine the chromosomal localization of the mouse PI3-Kinase p110alpha gene. FISH results and DAPI banding demonstrated localization of the p110alpha gene to band B on mouse chromosome 3, a region syntenic with human chromosome 3q26.3.     

The T cell receptor beta chain genes are located on chromosome 6 in mice and chromosome 7 in humans

Homologous clones that encode the beta chain of the T cell antigen receptor have been isolated recently from both murine and human cDNA libraries. These cDNA clones have been used in connection with interspecies hybrid cell lines to determine that the murine T cell receptor gene is located on chromosome 6 and the human gene on chromosome 7. In situ hybridization confirms these data and further localizes these genes to band B of chromosome 6 in the mouse and bands 7p13-21 in the human genome. The organization of the T cell antigen receptor J beta gene segments and C beta genes appears to be conserved, since very few intraspecies polymorphisms of restriction fragment length have been detected in either mouse or human DNA.     

The structural gene for the M1 subunit of ribonucleotide reductase maps to chromosome 11, band p15, in human and to chromosome 7 in mouse

The genes for the M1 subunit of the enzyme ribonucleotide reductase have been mapped in the human and the murine species by use of two independently derived mouse cDNA clones. Southern blot analysis of rodent x human somatic cell hybrid DNAs confirmed the assignment of RRM1 to the short arm of human chromosome 11. In situ hybridization to human metaphase chromosomes revealed a peak of silver grains over the distal third of band 11p15, a region corresponding to subbands p15.4----p15.5. The mouse Rrml locus was assigned to chromosome 7, where it forms part of a conserved syntenic group of at least seven other genes assigned to human chromosome band 11p15.     

Gene for a tissue-specific transcriptional activator (EBF or Olf-1), expressed in early B lymphocytes,adipocytes, and olfactory neurons,is located on human Chromosome 5, band q34, and proximal mouse Chromosome 11

Murine B lymphocytes, adipocytes, and olfactory neurons contain a DNA-binding protein that participates in the regulation of genes encoding tissue-specific components of signal transduction. Purification and cloning of this protein, termed early B-cell factor (EBF), from murine B lymphocytes and independent cloning of a protein, termed Olf-1, from olfactory neuronal cells revealed virtual complete amino acid sequence identity between these proteins. As a first step towards identifying a human genetic disorder or mouse mutation for which EBF could be a candidate gene, we have chromosomally mapped the corresponding locus in both species. By Southern hybridization analyses of somatic cell hybrid panels with murine cDNA probe, fluorescence chromosomal in situ hybridization (FISH) of human genomic clones, and analysis of recombinant inbred mouse strains, we have found single sites for EBF homologous sequences on human Chromosome (Chr) 5, band q34, and on proximal mouse Chr 11, in an evolutionarily conserved region.